Noradrenergic regulation in mouse supraoptic nucleus involves a nitric oxide pathway only to regulate arginine‐vasopressin expression and not oxytocin expression

Abstract

Noradrenalin (NA) regulates the expression of arginine-vasopressin (AVP) and oxytocin (OT) by magnocellular neurons in the supraoptic nucleus (SON) of the hypothamalus. Nitric oxide (NO) may be one of the factors involved in the NA signaling pathway regulating AVP and OT expression. To test this possibility, we used an ex vivo experimental model of mouse hypothalamus slices. Increases in AVP and OT levels in the SON were detected by immunohistochemistry and immunoenzyme assays after 1 hr and 4 hr incubations with NA (10(-4) M). There was also an increase in the expression and activity of neuronal NOS and inducible NOS in the SON as assessed by immunohistochemical and histoenzymological analysis of NADPH-diaphorase, whereas endothelial NOS was undetectable. To specify the role of NO, the slices were treated with NA and L-arginine methyl ester (L-NAME, an NOS inhibitor; 3 microM). This treatment for 1 hr abolished the NA-induced increase in AVP. Treatment with sodium nitroprusside (SNP, an NO donor; 0.1 mM) increased AVP levels, confirming that NO regulates AVP expression. Addition of 1 mM EGTA during the incubation with NA reduced the AVP increase by half, indicating that both nNOS and iNOS activities are involved in the regulation. A 1-hr treatment with L-NAME did not prevent the increase in OT induced by NA; similarly, treatment with SNP had no effect. These findings show that NO is involved in the regulation of AVP expression by NA and that NA control of OT expression is independent of NO.

Dp71 gene disruption alters the composition of the dystrophin-associated protein complex and neuronal nitric oxide synthase expression in the hypothalamic supraoptic and paraventricular nuclei

“…Because nNOS may be functionally related to DAPC (Tadayoni et al 2012), we analyzed its expression and activity after DP71 disruption. In wild-type mice, we confirmed previous reports of nNOS in the magnocellular neurons located in the dorsal part of the SON and in the lateral part of the PVN (Vacher et al 2003, Maolood et al 2007. nNOS expression was higher in the SON and PVN of Dp71-null mice, which is similar to what has been reported to occur in response to osmotic stimulation (Kadowaki et al 1994), hypovolemia (Ueta et al 1998), and noradrenalin treatment (Grange-Messent et al 2004, Maolood et al 2007.…”

“…These functions are fine-tuned by magnocellular activity, and among the different modulatory pathways, the NO pathway is particularly important (Antunes-Rodrigues et al 2004, Grange-Messent et al 2004, Maolood et al 2007. nNOS is expressed at high levels in the SON and PVN (Sagar & Ferriero 1987, Pasqualotto et al 1991, Arévalo et al 1992, Vincent & Kimura 1992) and its expression is functionally regulated by osmotic stimulation ( Kadowaki et al 1994, Villar et al 1994, Ueta et al 1998.…”

“…Indeed, in the hypothalamoneurohypophysis complex, NO is an important modulator of vasopressin synthesis and secretion (Yuan et al 2006, Raison et al 2011, St-Louis et al 2012. nNOS and NADPH diaphorase, the histochemical marker of NOS activity, are both present in magnocellular neurons (Grange-Messent et al 2004, Kadekaro 2004, Maolood et al 2007. Their expression levels and activity increase when magnocellular neuron activity increases in response to osmotic stimulation, dehydration, or hypovolemia (Kadowaki et al 1994, Villar et al 1994, Ueta et al 1995.…”

Differential involvement of noradrenaline and nitric oxide in the regulation of vasopressin and oxytocin expression in rat supraoptic nucleus

“…The expression of AVP and OT in mouse hypothalamus in vivo can be positively regulated by NA (Vacher et al, 2002). We confirmed these data using an ex vivo experimental model involving mouse hypothalamus slices (Maolood et al, 2007).…”

“…It modulates the activity of the main afferents to magnocellular neurons (Vacher et al, 2003). There is an NO pathway for a noradrenergic regulation only of AVP expression and not of OT expression in mouse SON (Maolood et al, 2007). Consistently with this work in mice, we previously demonstrated in rat magnocellular neurons short‐term interactions between NA and the activity and expression of NOS, enzymes implicated in the production of NO (Grange‐Messent et al, 2004): NA up‐regulates the neuronal and the inducible NOS in magnocellular neurons, this stimulation leading to NO production by these neurons.…”